Neuroprotective Role of Lactate Therapy in Humans With Traumatic Brain Injury
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Increase from baseline in brain extracellular lactate, pyruvate and glucose
研究概览
简要总结
Background: Although glucose is essential to cerebral function, abundant experimental and clinical evidence demonstrates that endogenously released lactate, rather than glucose, is the preferential energy substrate for the brain in conditions of stress and acute injury. In patients with severe Traumatic Brain Injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) monitored with cerebral microdialysis and brain tissue oxygen (PbtO2), our preliminary data show that increased brain extracellular lactate is frequently observed. Our findings indicate that elevated brain lactate more often occurs in the absence of brain hypoxia/ischemia and is mainly the consequence of increased cerebral glycolysis, i.e. it occurs in association with high extracellular pyruvate. These data suggest that the primary source of elevated lactate is activated glycolysis and strongly support the concept that endogenously released lactate can be utilized by the injured human brain as energy substrate. They prompt further investigation to examine whether exogenous lactate supplementation can be a valuable neuroprotective strategy after TBI or SAH. Indeed, in animal models of brain injury, administration of exogenous lactate improves neuronal and cognitive recovery.
Hypothesis: The investigators test the hypothesis that lactate therapy, administered during the acute phase of TBI or SAH, might exercise neuroprotective actions by restoring brain energetics and improving brain tissue PO2 and cerebral blood flow (CBF).
Aim of the study: The aim of this single-center study is to examine the effect of sodium lactate infusion on cerebral extracellular metabolites, brain tissue PO2 and cerebral blood flow, measured with CT perfusion and transcranial doppler (TCD).
Design: Prospective phase II interventional study examining the effect of a continuous 3-6 hours infusion of sodium lactate (20-40 µmol/kg/min), administered within 48 hours from TBI or SAH, on cerebral extracellular glucose, pyruvate, glutamate, glycerol, PbtO2 and CBF.
详细描述
Study: Prospective, single-centre phase II interventional study. The study will take place at the Department of Intensive Care Medicine, Lausanne University Medical Center (Centre Hospitalier Universitaire Vaudois, CHUV), Lausanne, Switzerland.
Patient population:
Patients will be monitored with an intra-parenchymal monitoring system, consisting of ICP (Codman®, Integra Neurosciences), PbtO2 (Licox®, Integra Neurosciences) and cerebral microdialysis (CMA Microdialysis®) catheters, based on the protocol for management of TBI presently in use at our center.
Each patient will receive a continuous infusion of sodium lactate (composition: lactate 1'000 mmol/L, Na 1'000 mmol/L: concentration 20-40 µmol/kg/min) for 3-6 hours. Sodium lactate will be prepared locally by the Pharmacie Centrale, CHUV, Lausanne.
Each patient will serve as his/her internal control, and the effect of sodium lactate on all brain physiological variables measured will be anayzed before, during and at the end of sodium lactate infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients admitted to our intensive care unit (ICU) after severe TBI or poor-grade aneurysmal subarachnoid hemorrhage (SAH), defined by a post-resuscitation Glasgow Coma Scale (GCS) < 9
- •Age 18-75 years
- •Abnormal head CT-scan (Marshall grade ≥ 2 or Fisher >2)
- •Intracranial pressure (ICP), PbtO2 and cerebral MD monitoring as part of standard care
排除标准
- •Penetrating TBI
- •non aneurysmal SAH
- •Age < 18 or > 75 years,
- •More than 1 extra-cranial injury with sustained hemodynamic instability and sustained blood lactate elevation > 4 mmol/L
- •Cognitive handicap due to previous neurological or neurosurgical history
- •Non-survivable injury, brain death or expected death within 48 hours
- •Pregnancy
研究组 & 干预措施
sodium lactate infusion
Continuous i.v. infusion of Sodium Lactate (2'400 mOsmol/L) over 3 hours
干预措施: sodium lactate infusion (Other)
结局指标
主要结局
Increase from baseline in brain extracellular lactate, pyruvate and glucose
时间窗: 6 hours
Increase from baseline in brain extracellular lactate, pyruvate and glucose measured with intra-parenchymal cerebral microdialysis catheter
次要结局
- Decrease from baseline in intracranial pressure(6 hours)
- Increase from baseline in brain tissue PO2(6 hours)
- Increase from baseline in cerebral perfusion pressure(6 hours)
- plasma sodium(6 hours)
- plasma osmolality(6 hours)
- mean CBF, measured by transcranial doppler(6 hours)
研究者
Mauro ODDO
médecin adjoint, PD-MER I
Centre Hospitalier Universitaire Vaudois